The meniscus is a fibrocartilage structure in the knee, between the femur and tibia and firmly anchored to the latter. It is more exact to distinguish between the medial or inner meniscus and the lateral or external meniscus. Meniscal fibrocartilage is often inexactly referred to as cartilage, and thought to have the same characteristics and properties as the hyaline cartilage encasing the joints. Actually, meniscal fibrocartilage differs significantly in structure and function from joint cartilage in general and that of the knee in particular, as described by Mow V. C. and co-workers (Structure and function of articular cartilage and meniscus. In: Mow V C, Hayes W C, editors. Basic Orthopedic Biomechanics. New York; 1991. p. 143-189).
The function of the meniscus is to match the two bones together, absorb shock and distribute weight evenly during the various stages of movement, from walking to running and jumping. Together with the hyaline cartilage, the menisci also reduce friction between the joint heads, while improving joint stability.
Pathologies of the meniscal tissue substantially involve partial or total lesions that may be caused by the knee being twisted abnormally with the foot firmly on the ground or by joint stress in athletes, and they normally lead to the breaking and/or progressive degeneration of the joint cartilage, ending in manifestations of arthrosis (Zamber et al., Arthroscopy, 1989; 5:258-268). This is due both to altered load distribution throughout the joint caused by meniscal lesions, and to the fact that vascularisation of the menisci is limited to their periphery (25-30%) and originates from the surrounding soft tissues, i.e. the synovial membrane and capsule. It is from this area alone that the repair processes can originate. Consequently, any damage involving the central part of the menisci is irreparable. Currently, three main methods are being used to treat meniscal lesions: meniscopexy; partial or total meniscectomy; graft.
Meniscopexy can be performed by arthroscopy and is indicated in cases where the meniscus is not broken, but where the vascularised meniscal wall has become dislodged from the joint capsule. The operation consists in stitching the meniscus to the capsule structures, with the formation of a fibrovascular scar that joins the margins of the wound together creating continuity with the adjacent meniscal fibrocartilage. The prognosis in such cases is often good, as the method exploits the capacity for repair of the only vascularised area in the menisci.
Conversely, there are currently no effective methods for treating lesions in the central, non-vascularised part of the meniscus.
In such cases, the alternative is to perform a meniscectomy, again by arthroscopy. This consists in partially or totally excising the meniscus, thus reducing the area of contact and altering the distribution of pressure on the joint. The resulting situation is one of increased strain and areas of persistent high pressure, especially on the tibial plate. This leads to a progressive degeneration of the knee cartilage, which seems to be proportional to the quantity of meniscus that has been removed (Fairbank T J et al., J Bone Jt Surg [Br], 1948, 30:664-670); the basic principle in this type of surgery is therefore to conserve as much of the functional tissue of the meniscus as possible.
When the extent of damage to the meniscus justifies total meniscectomy, the only alternative is to resort to a graft. There are various kinds of meniscus replacements (Farng E et al., Arthroscopy, 2004, 20:273-286; Peters G et al., Knee, 2003, 10:19-31), however, the traditional approach to recovering physiological function in damaged organs and tissues using replacements made of metal and/or ceramic materials or biological materials has intrinsic limitations, both biological, due to interaction with the organism and/or the possible transmission of pathologies, and mechanical, due to the obvious diversity between the mechanical properties of the replacements and those of the original tissue.
The need is therefore felt for meniscal prosthesis having the required mechanical resistance, but made of biologically compatible materials.
Hyaluronic acid (hereinafter referred to as “HA”) is a heteropolysaccharide constituted by D-glucuronic acid and N-acetyl-glucosamine, that is ubiquitous in the organism. HA plays multiple physiological roles, from support for the cells of numerous tissues to joint lubrication and modulation of numerous biological and physiological processes (such as cell proliferation, migration and differentiation), mediated by interaction with its membrane receptor CD44. Moreover, HA is a molecule that, when suitably modified by chemical reaction, gives rise to materials with the biological/physiological characteristics of the starting molecule but which can be processed in various ways, possibly also in association with other natural, semisynthetic or synthetic polymers, as described for example in EP 618 817 B1. The main chemical modifications that can be made to the HA according to the state of the art, are the following:    salification with organic and/or inorganic bases (EP 138 572 B1);    esterification (HYAFF®) with alcohols of the aliphatic, araliphatic, aromatic, cyclic and heterocyclic series (EP 216 453 B1);    inner esterification (ACP®) with a percentage of esterification not exceeding 20%;    amidation (HYADD™) with amines of the aliphatic, araliphatic, cycloaliphatic, aromatic, cyclic and heterocyclic series (EP 1 095 064 B1);    deacetylation on the fraction of N-acetyl-glucosamine (EP 1 312 772 B1);    O-sulphation (EP 702 699 B1);    percarboxylation (HYOXX™) by oxidation of the primary hydroxyl of the N-acetyl-glucosamine fraction (patent application No. EP 1 339 753).
Also known in the art is the possibility of using hyaluronic acid derivatives, possibly in association with natural and/or semisynthetic and/or synthetic polymers, for preparing three-dimensional structures (patent application EP 1 087 797). These structures are shaped as body parts, such as auricular or nasal septum, not intended for bearing load and strain. The process for preparing these structures requires to previously processing the hyaluronic acid derivatives in particular forms such as non-woven fabrics, porous structures or perforated membranes, which are then variously combined together to create the desired final structure. The mechanical properties of the resulting structures are not suitable for bearing loads, and even more to bear the mechanical strain to which the meniscal area is normally exposed. As to the composition of these structures, they are based on hyaluronic acid derivatives, whereas poly-εCaprolactone (PCL) is not mentioned. PCL is a hydrophobic polyester with excellent biocompatibility and low toxicity, the use of which has already been tried and tested in fields such as those of drug delivery (Sinha V R et al., Int J Pharm, 2004, 278:1-23) and tissue engineering (Kweon H et al., Biomaterials, 2003, 24:801-808). Nevertheless, this polymer has lengthy degradation times and does not have the necessary chemotactic characteristics for the interaction with cells; therefore, a prosthesis mainly constituted by poly-εCaprolactone would hinder the formation of meniscal fibrocartilage, and would be therefore completely unsuitable as meniscal prosthesis.
The need for meniscal prosthetic devices able to actually behave as a stable mechanical support allowing at the same time an effective regeneration of meniscal fibrocartilage, is therefore still felt.